We are using new methods for the noninvasive stimulation of the human cortex. Stimulation can be with a high-voltage electrical pulse or with magnetic stimulation. One purpose is to use these methods for noninvasive localization of different parts of the human cortex including motor cortex, sensory cortex and language cortex. Another purpose is to study cortical and corticospinal physiology in normal humans and in different disease states. We have continued to improve our techniques of topographical mapping with TMS. We are investigating CNS plasticity following lesions, finding new phenomena that have implications for theories of the organization of the motor system and mechanisms of reorganization. Exercise produces competing effects on corticospinal excitability. These effects are present in differing proportions in disorders producing fatigue. This phenomenon may yield an unambiguous marker for organic disease in patients complaining of fatigue. Motor evoked potential amplitudes increase prior to movement. Our experiments are yielding answers about how and where this change takes place. This is important in explaining how motor commands are generated and transmitted. Motor maps enlarge with acquisition of skills and motor learning. This process correlates closely with cognitive aspects of skill acquisition and learning, demonstrating the role of the primary motor cortex in the process. The physiology of the supplementary motor area (SMA) in humans is largely unexplored and its role in movement is controversial. Anatomical data suggest direct links with anterior horn cells. Our studies suggest a role both in the modulation of segmental reflexes and control of sequential movements. The pathophysiology of tics is mysterious. They are voluntary phenomena triggered by a pathological process. Our data suggest a means of altering this pathological desire to move.